Nephroprotective Effect of Milkfish, Patin, and Snakehead Fish Oil by Suppressing Inflammation and Oxidative Stress in Diabetic Rats

  • Heru Sasongko Universitas Sebelas Maret
  • Agung Endro Nugroho Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia.
  • Arief Nurrochmad Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia.
  • Abdul Rohman Center of Excellence, Institute for Halal Industry and Systems, Universitas Gadjah Mada, Yogyakarta, Indonesia
Keywords: Fish oil, nephroprotective, inflammation, oxidative stress


Diabetic nephropathy (DN) has been linked to a number of long-term problems caused by diabetes mellitus. Inflammatory and oxidative stress pathways contribute to DN development and progression. Many studies have shown the preventive advantages of diets rich in substances like anti-inflammatory and antioxidant elements like omega-3 fatty acids (n-3 FA) in preventing DN. Milkfish (Chanos chanos F.), patin (Pangasius micronema Blkr.), and snakehead fish (Chana striata Bloch) are types of fish oils that are known to contain n-3 FA. This study aims to prove the nephroprotective effect of the three types of fish oil in a rat model of diabetes mellitus. Thirty male rats were used in this study. The animals were randomly divided into six groups (n = 5): the non-diabetic group, the diabetes mellitus group, the diabetic with 150 mg/kg metformin orally group, the diabetic with 1000 mg/kg milkfish oil orally group, the diabetic with 1000 mg/kg patin fish oil orally group, and the diabetic with 1000 mg/kg snakehead fish oil orally group. Diabetes models were induced using 65 mg/kg streptozotocin and 230 mg/kg nicotinamide intraperitoneally. The test was carried out for 8 weeks, followed by the observation of the biochemical profiles of blood, urine, oxidative stress, and the immunohistochemistry of the kidneys. A normally and homogeneously distributed test followed by a one-way analysis of variance (ANOVA) and the LSD post hoc test were used to look at the data. At p≤0.05, the data was considered statistically significant. The results showed that serum creatinine levels did not differ significantly after the administration of milkfish, catfish, and snakehead fish oil for 8 weeks (p≥0.05). Different results were shown where the levels of serum BUN, uric acid, urine urea, and microalbumin urine were significantly different after administration of the three types of fish oil (p≤0.05). The same results were shown in oxidative stress (superoxide dismutase, glutathione, and malondialdehyde) and inflammation (interleukin-6 and tumor necrosis factor-α) profiles (p≤0.05). The conclusion is that milkfish, patin, and snakehead fish oils have moderate nephroprotection by suppressing inflammation and oxidative stress.


AlFaris, N. A., Alshammari, G. M., Alsayadi, M. M., AlFaris, M. A., & Yahya, M. A. (2020). Antidiabetic and antihyperlipidemic effect of Duvalia corderoyi in rats with streptozotocin-induced diabetes. Saudi Journal of Biological Sciences, 27(3), 925–934.
Allan, M., McCafferty, K., Sheaff, M., & Yaqoob, M. M. (2023). Identification and management of diabetic nephropathy. Medicine, 51(4), 262–268.
Araújo, L. S., Silva, M. V. da, Silva, C. A. da, Monteiro, M. L. R., Pereira, L. H. de M., Rocha, L. P., Corrêa, R. R. M., Reis, M. A., & Machado, J. R. (2016). Cytokines and T Helper Cells in Diabetic Nephropathy Pathogenesis. Journal of Diabetes Mellitus, 06(04), Article 04.
Araújo, L. S., Torquato, B. G. S., da Silva, C. A., dos Reis Monteiro, M. L. G., dos Santos Martins, A. L. M., da Silva, M. V., dos Reis, M. A., & Machado, J. R. (2020). Renal expression of cytokines and chemokines in diabetic nephropathy. BMC Nephrology, 21(1), 308.
Aryaie, M., Sharifi, H., Saber, A., Salehi, F., Etminan, M., Nazemipour, M., & Mansournia, M. A. (2022). Longitudinal causal effect of modified creatinine index on all-cause mortality in patients with end-stage renal disease: Accounting for time-varying confounders using G-estimation. PLOS ONE, 17(8), e0272212.
Bhatti, J. S., Sehrawat, A., Mishra, J., Sidhu, I. S., Navik, U., Khullar, N., Kumar, S., Bhatti, G. K., & Reddy, P. H. (2022). Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radical Biology and Medicine, 184, 114–134.
Bonilla-Méndez, J. R., Hoyos-Concha, J. L., Bonilla-Méndez, J. R., & Hoyos-Concha, J. L. (2018). Methods of extraction refining and concentration of fish oil as a source of omega-3 fatty acids. Ciencia y Tecnología Agropecuaria, 19(3), 645–668.
Brosius, F. C., Alpers, C. E., Bottinger, E. P., Breyer, M. D., Coffman, T. M., Gurley, S. B., Harris, R. C., Kakoki, M., Kretzler, M., Leiter, E. H., Levi, M., McIndoe, R. A., Sharma, K., Smithies, O., Susztak, K., Takahashi, N., & Takahashi, T. (2009). Mouse Models of Diabetic Nephropathy. Journal of the American Society of Nephrology : JASN, 20(12), 2503–2512.
Cohen, J. B., Tewksbury, C. M., Torres Landa, S., Williams, N. N., & Dumon, K. R. (2019). National Postoperative Bariatric Surgery Outcomes in Patients with Chronic Kidney Disease and End-Stage Kidney Disease. Obesity Surgery, 29(3), 975–982.
de Assis, A. M., Rech, A., Longoni, A., da Silva Morrone, M., de Bittencourt Pasquali, M. A., Perry, M. L., Souza, D. O., & Moreira, J. C. (2015). Dietary n-3 polyunsaturated fatty acids revert renal responses induced by a combination of 2 protocols that increase the amounts of advanced glycation end product in rats. Nutrition Research, 35(6), 512–522.
Donadio, J. V. J., Grande, J. P., Bergstralh, E. J., Dart, R. A., Larson, T. S., Spencer, D. C., & Group, T. M. N. C. (1999). The Long-Term Outcome of Patients with IgA Nephropathy Treated with Fish Oil in a Controlled Trial. Journal of the American Society of Nephrology, 10(8), 1772.
El-Boshy, M., Alsaegh, A., Qasem, A. H., Sindi, R. A., Abdelghany, A. H., Gadalla, H., Reda, D., Azzeh, F., Idris, S., Ahmad, J., & Refaat, B. (2021). Enhanced renoprotective actions of Paricalcitol and omega-3 fatty acids co-therapy against diabetic nephropathy in rat. Journal of Advanced Research.
Fathy, S. A., Mohamed, M. R., Ali, M. A. M., EL-Helaly, A. E., & Alattar, A. T. (2019). Influence of IL-6, IL-10, IFN-γ and TNF-α genetic variants on susceptibility to diabetic kidney disease in type 2 diabetes mellitus patients. Biomarkers, 24(1), 43–55.
Ghasemi Fard, S., Wang, F., Sinclair, A. J., Elliott, G., & Turchini, G. M. (2019). How does high DHA fish oil affect health? A systematic review of evidence. Critical Reviews in Food Science and Nutrition, 59(11), 1684–1727.
Gong, Y., Guo, X., & Zhu, Q. (2022). Nephroprotective properties of chitosan/sodium lignosulfonate/Au nanoparticles in streptozotocin-induced nephropathy in mice: Introducing a novel therapeutic drug for the treatment of nephropathy. Arabian Journal of Chemistry, 15(6), 103761.
Guo, Y., Hu, M., Ma, J., Chinnathambi, A., Alharbi, S. A., Shair, O. H. M., & Ge, P. (2021). Protective effect of panaxydol against repeated administration of aristolochic acid on renal function and lipid peroxidation products via activating Keap1-Nrf2/ARE pathway in rat kidney. Journal of Biochemical and Molecular Toxicology, 35(1), e22619.
Haligur, M., Topsakal, S., & Ozmen, O. (2012). Early Degenerative Effects of Diabetes Mellitus on Pancreas, Liver, and Kidney in Rats: An Immunohistochemical Study. Journal of Diabetes Research, 2012, e120645.
Han, E., Yun, Y., Kim, G., Lee, Y., Wang, H. J., Lee, B.-W., Cha, B. S., Kim, B. S., & Kang, E. S. (2016). Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia. PLOS ONE, 11(5), e0154683.
Hidayah, N., Rohman, A., Mustafidah, M., & Irnawati. (2022). Physicochemical characterization and fatty acid profiles of fish oil from milkfish (Chanos chanos F.). Food Research, 6(2), 265–270. Scopus.
Iseki, K., Ikemiya, Y., & Fukiyama, K. (1997). Risk factors of end-stage renal disease and serum creatinine in a community-based mass screening. Kidney International, 51(3), 850–854.
Itsiopoulos, C., Marx, W., Mayr, H. L., Tatucu-Babet, O. A., Dash, S. R., George, E. S., Trakman, G. L., Kelly, J. T., Thomas, C. J., & Brazionis, L. (2018). The role of omega-3 polyunsaturated fatty acid supplementation in the management of type 2 diabetes mellitus: A narrative review. Journal of Nutrition & Intermediary Metabolism, 14, 42–51.
Keapai, W., Apichai, S., Amornlerdpison, D., & Lailerd, N. (2016). Evaluation of fish oil-rich in MUFAs for anti-diabetic and anti-inflammation potential in experimental type 2 diabetic rats. The Korean Journal of Physiology & Pharmacology, 20(6), 581–593.
Kishore, L., Kaur, N., & Singh, R. (2017). Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy. Journal of Food and Drug Analysis, 25(3), 576–588.
Liu, J.-D., Liu, W.-B., Zhang, D.-D., Xu, C.-Y., Zhang, C.-Y., Zheng, X.-C., & Chi, C. (2020). Dietary reduced glutathione supplementation can improve growth, antioxidant capacity, and immunity on Chinese mitten crab, Eriocheir sinensis. Fish & Shellfish Immunology, 100, 300–308.
Mozaffarian, D., & Wu, J. H. Y. (2012). (n-3) Fatty Acids and Cardiovascular Health: Are Effects of EPA and DHA Shared or Complementary? The Journal of Nutrition, 142(3), 614S-625S.
Nadhiro, U., Subekti, S., Tjahjaningsih, W., & Patmawati. (2018). Quality characteristics of Bali sardinella (Sardinella lemuru) oil purified with bentonite as an adsorbent. IOP Conference Series: Earth and Environmental Science, 137, 012012.
Nugent, J., Aklilu, A., Yamamoto, Y., Simonov, M., Li, F., Biswas, A., Ghazi, L., Greenberg, J. H., Mansour, S. G., Moledina, D. G., & Wilson, F. P. (2021). Assessment of Acute Kidney Injury and Longitudinal Kidney Function After Hospital Discharge Among Patients With and Without COVID-19. JAMA Network Open, 4(3), e211095.
Persson, F., & Rossing, P. (2018). Diagnosis of diabetic kidney disease: State of the art and future perspective. Kidney International Supplements, 8(1), 2–7.
Putri, A. R., Rohman, A., & Riyanto, S. (2019). Comparative study of fatty acid profiles in patin (Pangasius micronemus) and gabus (Channa striata) fish oil and its authentication using FTIR spectroscopy combined with chemometrics. International Journal of Applied Pharmaceutics, 55–60.
Rahmani, A., Maleki, V., Niknafs, B., Tavakoli-Rouzbehani, O. M., & Tarighat-Esfanjani, A. (2022). Effect of Nigella sativa supplementation on kidney function, glycemic control, oxidative stress, inflammation, quality of life, and depression in diabetic hemodialysis patients: Study protocol for a double-blind, randomized controlled trial. Trials, 23(1), 111.
Sagoo, M. K., & Gnudi, L. (2018). Diabetic nephropathy: Is there a role for oxidative stress? Free Radical Biology and Medicine, 116, 50–63.
Samsu, N. (2021). Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment. BioMed Research International, 2021, e1497449.
Sasongko, H., Efendi, N. R., Budihardjo, A., Farida, Y., Amartiwi, T., Rahmawati, A. A., Wicaksono, A., & Sugiyarto. (2017). Solvent and extraction methods effects on the quality of eel ( Anguilla bicolor ) oil. Journal of Physics: Conference Series, 795(1), 012021.
Sasongko, H., Efendi, N. R., & Sugiyarto. (2018). The ethanolic extract of mountain papaya (Vasconcellea pubescens A.DC.) fruit against lipid peroxidation of rat liver tissues. AIP Conference Proceedings, 2019(1), 050001.
Sasongko, H., Nurrochmad, A., Nugroho, A. E., & Rohman, A. (2022). Indonesian freshwater fisheries’ oil for health and nutrition applications: A narrative review. Food Research, 6, 501–511.
Sasongko, H., Nurrochmad, A., Rohman, A., & Nugroho, A. E. (2022). Characteristic of Streptozotocin-Nicotinamide-Induced Inflammation in A Rat Model of Diabetes-Associated Renal Injury. Open Access Macedonian Journal of Medical Sciences, 10(T8), 16–22.
Sathibabu Uddandrao, V. V., Brahmanaidu, P., Ravindarnaik, R., Suresh, P., Vadivukkarasi, S., & Saravanan, G. (2019). Restorative potentiality of S-allylcysteine against diabetic nephropathy through attenuation of oxidative stress and inflammation in streptozotocin–nicotinamide-induced diabetic rats. European Journal of Nutrition, 58(6), 2425–2437.
Sayed, A. A. R. (2012). Ferulsinaic Acid Modulates SOD, GSH, and Antioxidant Enzymes in Diabetic Kidney. Evidence-Based Complementary and Alternative Medicine, 2012, e580104.
Shapiro, H., Theilla, M., Attal-Singer, J., & Singer, P. (2011). Effects of polyunsaturated fatty acid consumption in diabetic nephropathy. Nature Reviews Nephrology, 7(2), Article 2.
Singh, B., Kumar, A., Singh, H., Kaur, S., Kaur, S., Singh Buttar, H., Arora, S., & Singh, B. (2020). Zingerone produces antidiabetic effects and attenuates diabetic nephropathy by reducing oxidative stress and overexpression of NF-κB, TNF-α, and COX-2 proteins in rats. Journal of Functional Foods, 74, 104199.
Sugata, M., Wiriadi, P. F., Lucy, J., & Jan, T. T. (2019). Total lipid and omega-3 content in Pangasius catfish (Pangasius pangasius) and milkfish (Chanos chanos) from Indonesia. Malaysian Journal of Nutrition, 25(1), 163–170. Scopus.
Szeto, H. H. (2006). Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents. The AAPS Journal, 8(3), 62.
Tsai, H.-J., Kuo, F.-C., Wu, C.-F., Sun, C.-W., Hsieh, C.-J., Wang, S.-L., Chen, M.-L., Hsieh, H.-M., Chuang, Y.-S., & Wu, M.-T. (2021). Association between two common environmental toxicants (phthalates and melamine) and urinary markers of renal injury in the third trimester of pregnant women: The Taiwan Maternal and Infant Cohort Study (TMICS). Chemosphere, 272, 129925.
Usta, M., Ersoy, A., Ersoy, C., Ayar, Y., Goksel, G., & Karagoz, I. S. (2020). Effect of omega-3 polyunsaturated fatty acid supplementation on glycemic control and renal function in type 2 diabetic patients with chronic kidney disease. Acta Medica Mediterranea, 36(2), 821–828.
Vitlov Uljević, M., Starčević, K., Mašek, T., Bočina, I., Restović, I., Kević, N., Racetin, A., Kretzschmar, G., Grobe, M., Vukojević, K., Saraga-Babić, M., & Filipović, N. (2019). Dietary DHA/EPA supplementation ameliorates diabetic nephropathy by protecting from distal tubular cell damage. Cell and Tissue Research, 378(2), 301–317.
Yoo, D., Jung, E., Noh, J., Hyun, H., Seon, S., Hong, S., Kim, D., & Lee, D. (2019). Glutathione-Depleting Pro-Oxidant as a Selective Anticancer Therapeutic Agent. ACS Omega, 4(6), 10070–10077.
How to Cite
Sasongko, H., Endro Nugroho , A., Nurrochmad, A., & Rohman, A. (2024). Nephroprotective Effect of Milkfish, Patin, and Snakehead Fish Oil by Suppressing Inflammation and Oxidative Stress in Diabetic Rats . Indonesian Journal of Pharmacy, 35(1), 63-73.
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